Hypothalamic fMRI response to nutrients

下丘脑功能磁共振成像对营养物质的反应

• 批准号: 7213783
• 负责人: JONATHAN Q. PURNELL
• 金额: $ 20.22万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-20 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7213783
• 关键词: bioimaging /biomedical imaging; body weight; brain electrical activity; brain stem; clinical research; dietary lipid; fructose; functional magnetic resonance imaging; glucose; human subject; hypothalamus; intravenous administration; neuroregulation; nutrient intake activity; nutrition related tag; obesity; pathogenic diet; statistics /biometry; weight gain

DESCRIPTION (provided by applicant): Animal studies have established the importance of the hypothalamus in the control of appetite and energy expenditure. Nuclei within this area of the brain integrate inputs from adipose tissue reflecting body fat stores and the gastrointestinal tract reflecting the amount and types of food ingested. These afferent signals trigger changes in food intake and energy expenditure through mechanisms involving both immediate alterations in neuronal cell electrical activity and relatively slower effects mediated via hormone-receptor binding. While these concepts of a central integrative center controlling weight regulation are well studied in animal models, the importance of these findings to humans is less clear. This is in large part due to a lack of tools available to study neuronal responses to various effectors in-vivo in humans. Functional nuclear magnetic imaging (fMRI) is a non-invasive, non-radioactive imaging technique that detects real-time changes in neuronal electrical activity to within a few millimeters in the brain. fMRI has been used to study the brain's response to ingestion of glucose and shown differences in this response between lean and obese subjects. However, questions remain regarding the specificity of these differences for nutrients (as opposed to gut hormones) and interactions of different macronutrients with central centers involved in weight regulation in humans. The proposals in this pilot grant will bring together investigators with backgrounds in clinical research, basic electrophysiological and neuroendocrine mechanisms of obesity, and fMRI imaging to better understand how nutrients affect brain activity in hypothalamic and brainstem regions involved with weight regulation in humans. The first aim will use fMRI to determine hypothalamic and brainstem responses to intravenous glucose and fructose in lean and obese subjects. The second aim will determine if lipids affect central glucose responsiveness as suggested by weight gain on high-fat diets in rodent models. Experience and data gained from these studies will be used in future proposals of effects on brain activity to mixed meals, long-term feeding of diets of differing macronutrient content, as well as to infusions of individual and combinations of gut-derived hormones secreted in response to meals and adipocyte hormones such as leptin. Simultaneous sampling of blood for levels of nutrients, insulin, leptin, and other hormones involved in weight regulation will give insight into the role they may play in changes in fMRI signaling in weight regulation centers in the brain. Lay Description: This study will use functional MRI scanning to explore how the brain is affected by sugar and fat. These studies will help us to better understand why changes in the diet might lead to weight gain or loss.

描述（由申请人提供）：动物研究确定了下丘脑在控制食欲和能量支出中的重要性。大脑该区域内的核从脂肪组织中整合了反映人体脂肪储存的输入，胃肠道反映了摄入的食物的数量和类型。这些传入信号通过涉及神经元细胞电活动的立即改变和通过激素受体结合介导的效应的机制引发食物摄入和能量消耗的变化。尽管在动物模型中对控制体重调节的中央集成中心的这些概念进行了很好的研究，但这些发现对人类的重要性尚不清楚。这在很大程度上是由于缺乏用于研究人类对各种效应子的神经元反应的工具。功能性核磁成像（fMRI）是一种非侵入性的非放射性成像技术，可检测到大脑中几毫米内神经元电活动的实时变化。 fMRI已用于研究大脑对葡萄糖摄入的反应，并显示出瘦和肥胖受试者之间这种反应的差异。然而，关于这些差异在营养（而不是肠道激素相反）的特异性以及不同大量营养素与与人类体重调节有关的中心中心的相互作用的问题仍然存在。该试点赠款中的建议将使研究人员在临床研究，肥胖症的基本电生理和神经内分泌机制以及fMRI成像中的背景汇集在一起​​，以更好地了解营养如何影响与人类体重调节体重调节的下丘脑和脑干区域的脑活动。第一个目的将使用fMRI来确定瘦和肥胖受试者中对静脉葡萄糖和果糖的下丘脑和脑干反应。第二个目的将确定脂质是否会影响啮齿动物模型中高脂饮食的体重增加所暗示的中央葡萄糖反应能力。这些研究从这些研究中获得的经验和数据将用于对脑活动的影响，对混合餐的影响，不同大量营养素含量的饮食的长期喂养，以及为饮食和脂肪细胞激素（如瘦素）分泌的肠道激素的输注以及肠道衍生的激素的组合。同时对体重调节的营养水平，胰岛素，瘦素和其他激素的血液进行采样，将洞悉它们在大脑体重调节中心中fMRI信号传导变化中的作用。外表描述：本研究将使用功能性MRI扫描来探索大脑如何受糖和脂肪的影响。这些研究将帮助我们更好地理解饮食的变化为什么会导致体重增加或减肥。